The heme-binding protein HbpS regulates the activity of the Streptomyces reticuli iron-sensing histidine kinase SenS in a redox-dependent manner.
The SenS/SenR system of Streptomyces reticuli regulates the expression of the redox regulator FurS, the catalase-peroxidase CpeB and the heme-binding protein HbpS. SenS/SenR is also proposed to participate in sensing redox changes, mediated by HbpS. Here, we show in vitro that heme-free HbpS represses the autokinase activity of SenS; whereas hemin-treated HbpS considerably enhances SenS autophosphorylation under redox conditions using either H(2)O(2) or DTT. The presence of iron ions alone or in combination with H(2)O(2) or DTT also leads to significantly increased phosphorylation levels of SenS. Further comparative physiological studies using the S. reticuli WT, a S. reticuli hbpS mutant and a S. reticuli senS-senR mutant corroborates the importance of HbpS and the SenS/SenR system for resistance against high concentrations of iron ions and hemin in vivo. Hence SenS/SenR and HbpS act in concert as a novel three-component system which detects redox stress, mediated by iron ions and heme.
Bogel
Gabriele
G
FB Biologie/Chemie, Angewandte Genetik der Mikroorganismen, Universität Osnabrück, Barbarastr. 13, 49069, Osnabrück, Germany.
Schrempf
Hildgund
H
Ortiz de Orué Lucana
Darío
D
D001426:Bacterial Proteins / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D000071677:Histidine Kinase; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010544:Peroxidases / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013302:Streptomyces / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D014131:Trace Elements / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; C119258:FurS protein, Streptomyces reticuli; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D016877:Oxidants; D014131:Trace Elements; D014157:Transcription Factors; D006427:Hemin; D006861:Hydrogen Peroxide; D007501:Iron; D010544:Peroxidases; C081610:catalase-peroxidase, bacteria; D011494:Protein Kinases; D000071677:Histidine Kinase; D004229:Dithiothreitol